Acne vulgaris is an illness that afflicts adolescents and young adults. About 20% of those with acne, who seek medical care, are severe enough to require systemic therapy. Those on antibiotics receive about 9.7 million prescriptions for oral antibiotics and about 8.2 million for the topical antibiotics. Therapy frequently continues for more than 6 months. Simply stated, very large quantities of antibiotics are used for an extended period of time by this sector of the population. The burden of both acne and acne therapies, as with all skin diseases, on society and the patient has not been well described as discussed at a recent NIAMS conference. We have recently demonstrated that antibiotic therapy for acne when given topical and/or orally to young adults may profoundly affect an individual's likelihood of being colonized with group A streptococcus (GAS), the main bacterial cause of pharyngitis. Upper respiratory tract infections, including pharyngitis, are extraordinarily common acute medical problems that are primarily of viral origin, are self-limited acute condition, and are generally mild but have huge public health implications due to the shear magnitude of numbers of individuals afflicted. In fact, the US economic cost is estimated to be more than 25 billion dollars per year. There are very few natural models of truly long-term human antibiotic use. Acne is a model of a disease for which long-term antibiotic use is standard and appropriate therapy. In this proposal, we will explore possible mechanisms that may be responsible for the increase in oro-pharyngeal colonization of GAS that we have noted in individuals who use antibiotics (oral and/or topical) for acne. We believe that the antimicrobial effect is through the elimination of competing normal bacterial flora. In fact, GAS in the oro-pharynx has been shown to be "regulated" by another organism, like S. Salivarius. Epidemiologically, very little is known about the association of changes in the normal flora of the throat and how this may impact the acquisition and chronic carriage of GAS, or whether these changes are associated with an infectious illness (i.e., pharyngitis). Persistent colonization, potentially does not only put the patient at risk but increases the risk of spread of GAS to close contacts. Persistent colonization of GAS also increases the likelihood of GAS acquiring resistance directly and horizontally from related species. Finally, with respect to bioterrorism post-exposure prophylaxis with antibiotics such as the tetracyclines, which are used to treat acne, will need to be maintained for prolonged periods of time (6 to 8 months). There is currently very limited data on the long-term consequences of tetracycline use. With respect to all of these issues, acne patients represent a great model to study regarding both the long-term toxicity of antibiotics and the risks of increasing resistance among bacterial pathogens exposed to drugs during treatment. We hypothesize that the use of long-term antibiotics for acne can result in oropharyngeal colonization with GAS and that this colonization can result in morbidity. To that end, we describe studies to help us understand who is at risk for colonization with GAS, the likelihood that these individuals will be persistently colonized, and the likelihood that individuals on antibiotics will develop pharyngitis.